Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-4-19
pubmed:abstractText
The cytokine tumor necrosis factor-alpha (TNF-alpha) plays an important role in endothelial injury, which is associated with the release of reactive oxygen species and the induction of apoptosis. We report on our study of TNF-alpha-induced apoptosis in human coronary artery endothelial cells and its modulation by the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand pioglitazone. Treatment of cells with TNF-alpha (40 ng/mL) resulted in apoptosis as measured by DNA laddering and caspase-3 activation. TNF-alpha treatment decreased the expression of antiapoptotic protein Bcl-2 (P <.05 vs control), but not the expression of Fas or FLIP, in human coronary artery endothelial cells. Treatment of cells with TNF-alpha also enhanced lipid peroxidation (P <.01 vs control). Pretreatment of cells with the PPAR-gamma ligand pioglitazone blocked TNF-alpha-mediated apoptosis, caspase-3 activation, expression of Bcl-2, and lipid peroxidation (P <.01 vs TNF-alpha alone). These results indicate that TNF-alpha induces oxidative stress in human coronary artery endothelial cells, resulting in apoptosis through a reduction in Bcl-2 expression and the subsequent activation of caspase-3. The PPAR-gamma ligand pioglitazone modulates lipid peroxidation, alters Bcl-2 expression and caspase-3 activation, and finally reduces apoptosis. The antioxidant and antiapoptotic effects of pioglitazone may be the mechanism by which this agent reduces endothelial injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1074-2484
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-41
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Tumor necrosis factor-alpha-induced apoptosis of human coronary artery endothelial cells: modulation by the peroxisome proliferator-activated receptor-gamma ligand pioglitazone.
pubmed:affiliation
Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205-7199, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't